Transformable nano-antibiotics for mechanotherapy and immune activation against drug-resistant Gram-negative bacteria

Abstract

The dearth of antibiotic candidates against Gram-negative bacteria and the rise of antibiotic resistance create a global health concern. The challenge lies in the unique Gram-negative bacterial outer membrane that provides the impermeable barrier for antibiotics and sequesters antigen presentation. We designed a transformable nano-antibiotics (TNA) that can transform from nontoxic nanoparticles to bactericidal nanofibrils with reasonable rigidity (Young’s modulus, 21.6 ± 5.9 MPa) after targeting β-barrel assembly machine A (BamA) and lipid polysaccharides (LPSs) of Gram-negative bacteria. After morphological transformation, the TNA can penetrate and damage the bacterial envelope, disrupt electron transport and multiple conserved biosynthetic and metabolic pathways, burst bacterial antigen release from the outer membrane, and subsequently activate the innate and adaptive immunity. TNA kills Gram-negative bacteria in vitro and in vivo with undetectable resistance through multiple bactericidal modes of action. TNA treatment–induced vaccination results in rapid and long-lasting immune responses, protecting against lethal reinfections.

Organic–Inorganic Heterointerface-Expediting Electron Transfer Realizes Efficient Plasmonic Catalytic Sterilization via a Carbon-Dot Nanozyme

“…coli and Gram-positive S. aureus, place an enormous burden on public health and the social economy owing to their high invasiveness and ubiquity in daily life. , In view of the excellent plasmonic catalysis and localized heating of the FeCG nanozyme, we first investigated the antibacterial activity of plasmonic FeCG against E. coli and S.…”

Urchin-like Fe3O4@Bi2S3 Nanospheres Enable the Destruction of Biofilm and Efficiently Antibacterial Activities

“…However, the poor penetration of the nanomaterials into biofilm greatly limited the efficiency of combating BAIs. − Various strategies have been developed to enhance the permeability of nanostructures, including controlling the size and shape, , polymer-targeted modification, − matrix component-degrading enzyme decoration, − liposome encapsulation, − and polypeptide modification. − Nanoparticles with sharp shapes were more likely to destroy the substrate structure of biofilm than blunt particles. , Recently, Qian et al synthesized a magnetic zeolitic imidazolate framework (ZIF) with a flower-like clustered structure for combating biofilm infections via combining the photothermal with catalytic properties, which demonstrated that the flower-like structure could destroy the local biofilm structure to increase the penetration . In addition, the sharp-shaped nanostructures equipped with magnetic nanoparticles provided enormous potential for biofilm destruction. − Magnetic nanoparticles tunneled channels into the biofilm under an alternating magnetic field (AMF), thus improving the permeability of the antibacterial agent.…”

“…35−38 Nanoparticles with sharp shapes were more likely to destroy the substrate structure of biofilm than blunt particles. 39,40 Recently, Qian et al synthesized a magnetic zeolitic imidazolate framework (ZIF) with a flower-like clustered structure for combating biofilm infections via combining the photothermal with catalytic properties, which demonstrated that the flowerlike structure could destroy the local biofilm structure to increase the penetration. 41 In addition, the sharp-shaped nanostructures equipped with magnetic nanoparticles provided enormous potential for biofilm destruction.…”

Inhaled immunoantimicrobials for the treatment of chronic obstructive pulmonary disease

“…However, their efficacy is often suboptimal because of insufficient entry into bacteria and the occurrence of drug resistance (10)(11)(12)(13)(14). For instance, Pseudomonas aeruginosa, a causative pathogen of exacerbations in patients with severe COPD, has a low-permeability outer membrane, which limits the penetration of antibiotics into the cells (15,16). Antimicrobial peptides (AMPs) and AMP mimics, which typically consist of cationic and hydrophobic amino acid residues, serve as important alternatives to antibiotics and can kill bacteria by directly destabilizing/ disrupting their membranes (17).…”